HU227477B1 - Solid, quick dissolving pharmaceutical compositions containing cetrizine - Google Patents

Description

S & xláxd, gyoxsaa disintegrating bayxrxzi <: ^ wise.ényék

The present invention relates to solid, rapidly disintegrating cetirizine effervescent formulations in the form of soluble tablets, dispersible tablets or granules.

Cetirizine, a 4- (diphenylmethyl) -piperidino-alkoxy-acetic acid derivative having antiallergic and antispasmodic properties, is described in EF 058 14 6. E.P 294 993, WO 92/02212 and EP 35 '? It discloses 350 tablets and capsule-shaped formulations of ethersin which are released in a controlled or continuous manner. Oral or nasal formulations, e.g. cough suppressant fluids - described in WO-94/08351.

Cetirizine solutions for ophthalmic and nasal use are disclosed in EP 505 203. The patent literature describes oral administration forms with at least one liquid flavoring layer, e.g. surrounded by menthol / 00 94/25009 / and freeze-dried dosage forms containing a taste-masking matrix. present (EP 538 355;

EP 548 355 industry discloses icular tablets having a disintegration rate in the oral cavity or tongue of less than 50 seconds; they contain the active ingredient in the form of coated microcrystals or microgranules to mask the muscle.

WO 95/07707 discloses effervescent granules based on chelated carbonate and citric acid for the preparation of a pharmaceutical composition; a ·>

Φφ ΦΦφΦ ΦΦΧΦ ΦΦΦ φ φφφ φ φ »φφ

Legalább * φ φ Φ legalább at least one other edible acid, eg 5-20 parts by weight of citric acid. malic acid can be used.

EB 636 364 relates to a highly soluble dosage form; it consists of active substance particles coated with a lozenge, a water-soluble combinable carbohydrate and a binder.

The tablets disintegrate in the mouth within 30 seconds after oral administration, so that the coated drug particles can be swallowed by the patient before release.

As a carbohydrate, e.g. mannitol, dextrose or lactose and cellulose acetate or hydroxypropylmethylcellulose as flavoring agents.

EB 525 36 describes chewable tablets which are essentially a base of three bases: an organic acid, in particular an alkaline or alkaline earth metal of citric acid, and preferably only one. they contain edible organic acids, in particular alkaline acid and other auxiliaries, which have been partially converted into the alkali and / or alkaline-earth metal salts. Thus, a slight aftertaste of known lozenges or chewable tablets is avoided. In particular, the elimination of chalk isosals of lozenge or chewable tablets containing minerals is described. The bitter iz. however, no decrease was observed.

Cetirizine hydrochloride should not be used as an active ingredient in the preparation of solid compositions having a very bitter taste and a rapid disintegration. Cetirizine effervescent tablets are therefore not known in the art.

However, for a variety of reasons, however, soluble and dispersible tablet-shaped, particularly calcium-based, sparkling, are required. Ν y y y f f f f. * X · * · for the marketing of pharmaceutical products. On the one hand, especially. Older people may have problems taking the tablets. on the other hand, many patients swallowing! struggling ..

Some rapidly disintegrating effervescent formulations are also advantageous because they can be conveniently taken on the go without absorbing liquid. A major benefit of allergy is the simultaneous administration of calcium as an inorganic substance with antihistamines.

Concealing the bitter taste of A. cetirizine causes special problems. The aqueous solution of cetirizine HCl has an unpleasant, bitter taste.

Adding appropriate flavoring agents / 1. For example, EP 638 364 or US 5 178 878 makes the preparation process more complicated. In addition, the microencapsulated active ingredients have a much more difficult dispersibility.

A further disadvantage is that the actual active ingredient Illett requires a number of excipients to formulate the above Composition Mixture.

Currently, film-coated tablets and orally available solutions are commercially available. The film layer serves to cover the bitter taste. The solutions contain large amounts of sorbitol (450 mg serbit / 1 mg cetirizine).

SUMMARY OF THE INVENTION It is an object of the present invention to provide novel and therapeutically advantageous cefirlin-containing solid, rapidly disintegrating effervescent compositions.

In order to accomplish this object, the present invention relates to solid, rapidly disintegrating effervescent compositions for oral use which contain cetirizine or a pharmaceutically acceptable salt thereof.

Α-5 - ΑΦ α * salt, a effervescent base containing at least the edible organic acid of the brain and / or salts thereof with alkaline or alkaline earth metal carbonates or bicarbonates and optionally pharmaceutically acceptable excipients.

When water is added to the soluble or dispersible tablets or soluble granules of the invention, a solution or suspension is formed as carbon dioxide gas develops, which is very simply swallowing! it can also be taken in patients with difficulty.

This solution already has a pleasant taste on your surprising soda. This is particularly true in the case of effervescent formulations containing soluble calcium

Quickly disintegrating pills can be made into beds for immediate disintegration in the mouth,

The rapid release of the active ingredient is particularly important to facilitate rapid action,

Effervescent formulations containing various active ingredients and vitamins are known in the art. These effervescent compositions generally contain a carbon dioxide release agent and a carbon dioxide release agent. The carbon dioxide releasing agent is preferably an alkali carbonate or alkali hydrocarbonate, such as sodium carbonate or sodium bicarbonate. tablets with the active ingredient and the excipients.

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As an edible organic acid, e.g. hydrochloric acid, acetic acid, fumaric acid, adipic acid, succinic acid, ascorbic acid, maleic acid or citric acid may be used.

Pharmaceutically acceptable salts of acids, e.g. solid salts having at least one other acid function, such as sodium dihydrogen or disodium hydrogen phosphate or monosodium or disodium citrate.

Surprisingly, we have now found this, a tip of a sparkling wine: the sole application of a system, especially on a calcium basis, leads to the masking of the oetirizine active ingredient.

starvation does not require the costly coating of each active ingredient crystal to mask the bitter taste of the oethirizine.

Thus, for the first time, it is believed possible to produce effervescent compositions for use in the treatment of allergic diseases which contain the highly effective oethirizine.

It was not obvious to those skilled in the art to develop such solid, rapidly disintegrating formulations of oethirizine as this had previously been rendered impossible by the bitter taste of oethirizine.

Some experiments e.g. it was found that 10 mg of oethirizine dissolved in 60 ml of water was bitter (Fig. Ί).

If the composition of the invention is dissolved in the same volume of water, the solution will have a pleasant taste and can be ingested by the patient without any problem, thus substantially improving the acceptability,

Because of its chemical structure, oetirizine is an organic acid that can stimulate tg receptors, thereby increasing gastric acid secretion. The effervescent composition of the effervescent composition of the present invention may serve to prevent the resulting side effects,

In particular, the present invention relates to cetirizine propellant compositions in which the effervescent base comprises the following ingredients:

(a) A mixture of calcium carbonate and an acid on an edible organ

(b) a mixture of calcium carbonate, sodium carbonate, sodium bicarbonate and an edible organic acid

(c) a mixture of sodium carbonate, sodium bicarbonate and an edible organic acid.

The soluble or dispersible cetirizine tablets are il. the soluble granules contain 5-20 mg cetirizine and 50-5000 mg, preferably 500-3000 mg of effervescent base.

The effervescent base preferably contains from 100 to 500 mg of calcium ion, in the form of calcium carbonate, and from 20 to 1500 mg of citric acid and / or its salts. In a further preferred embodiment, the sparkling base comprises 50-2000 mg of sodium bicarbonate, 20-200 mg of sodium carbonate and 20-1500 mg of citric acid and / or 20-500 mg of tartaric acid,

A further preferred composition of the effervescent base A is 50-500 mg sodium bicarbonate, 20-100 mg sodium carbonate and 50-750 mg calcium carbonate, and 100-1500 mg citric acid.

The dispersible cetirizine effervescent tablets of the present invention also produce carbon dioxide, which further accelerates the disintegration of the tablets. In the case of soluble tablets, however, only less effervescent! activity can be observed.

The soluble or dispersible tablets can be prepared according to known methods for the preparation of effervescent bases, * * cetirizine, HCl effervescent mannitol PG 'pharmaceuticals DCL 21 peppermint flavor. According to the separate bed process, the acidic components are granulated with an aqueous or alcoholic solution of citric acid in aqueous or polyvinylpyrrolidone, and the calcium component A can be directly mixed with tableted calcium carbonate. The sodium carbonate, bicarbonate and alkaline earth metal carbonate component can be granulated separately, the other excipients of tablet A are homogeneously incorporated and the mass is tabletted in a suitable press,

However, other methods may also lead to a suitable product, such as granulation of the acidic and alkaline components with binder solutions, e.g., PVP or sugar alcohols. Other granulation methods, such as topogranulation, are also described.

The cetirizine formulations of the present invention could include flavoring and sweetening agents, as well as known pharmaceutical excipients such as polyethylene glycol, sodium benzoate, oleic acid and silicon dioxide.

The compositions of the present invention are described in more detail by way of examples, but are not intended to be limiting.

mg of effervescent tablets

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sparkling base: mg cltromsav K & K · 's- · sodium bicarbonate 200 tar carbonate 100 Sodium extras 0.5 ascorbic acid K s z a oha r i η - n á t r i nm. 800 2> example mg soluble tablets nntrlzin n á t r inam h i d r og en ka rboné t 2 0 0 extremsav 4 4 3 ascorbic acid *? κ ná t rí nm-ka rboná t ?> / * <K ^: v saccharin sodium nm t \ V mannitol 80 .1H KI '. O £ 70 014 3. ^ mg soluble granules cetirizine 10

sodium bicarbonate 200 oítromsav 730 k á1exnm-ka rbonát 230 ascorbic acid 25

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100 ms soluble tablet through rxnm-hi hydrogen carbonate citric acid 1 µm through aspartame sodium carbonate mannitol

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izjaBÉE. mg soluble granules cetirizine 10 calcium carbonate 750 citric acid 805 avicel 42 elves δ 2 5 maltodextrin 15 aspartame 3 aroma 20 2270 Example 7 mg dispersible tablets cetrióia 5 ka 1 c i um - ka r boa a t U. f λ {<v.- 'V polyvinylpyrrolidone j> r> citric acid G Ύ Γί xt> V avicel 20 maltodextrin 18 xylitol 500 aspartame ··> Λ. szacha ri.n - aá t r i lord 1 a r om a 15 ku ko r i c: starch 80

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φ * φ φ φ φφφ φφ * X * Φ X Φ Φ φ φ φ Φφ φχφ X 3. ^ mg ..di dispersible tabletha ce is on guard, η 10 ka 1c1nm- ka rfoon á t 500 polyvinyl pírrolldón .1. i eitrcrasav 160 avicel 15 mannitol 430 rnaitodeztrin 18 aspartame • 7 aroma .15 1,167 Example 9. mg diszperoáIható tablet cetirizine 10 ka 1 c i nm - k a r b ο n á t 300 óitromsav . ·. * <·; trio 17 mannitol 250 sta ltoúextrir. 6 aspartame 1 hardened castor oil 21 <5 .COILS 8 645 Example 10. mg dlszpergáIható chewable tablets cetirizine 5 k a 1 e i o m- ka r b ο n á t 750 EtOC 37

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aercszl 1. 180 mann.it. 1.13 citric acid 123 ma Itoaex.tr in 23 Avic 87 aszpax'tám S peppermint aroma 8 orange aroma '7 n 2.333 Example XI mg dispersible chewable tablets catrizin 10 calcium carbonates of 750 EtOC 3? aeresz11 100 mannitol 1130 citric acid 123 maitodex.tr in. 23 avicel 37 aspartame 5 peppermint aroma 3 orange aroma 70 2.333 12th mg Dispensable Chewable Tablets cetirizine 5 calcium. ··· carbonate 750 endragit E 37 aerosz.il 100

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Φφ φ χ φ φ φ φ φ φ φ φφ mannititic citric acid ma ltodextrin avicéi aspartame orange aroma

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Claims (11)

.1. Solid, rapidly disintegrating effervescent compositions comprising orally administered cetirizine or pharmaceutically acceptable salts thereof, a effervescent base containing at least one edible organic acid and / or salts thereof, alkaline and / or alkaline earth metal carbonates, and optionally pharmaceutically acceptable excipients. 2, Effervescent tablets, dispersible tablets or soluble granules according to claim 1. The effervescent composition according to claims 1 and 2, comprising 5 to 20 mg cetirizine or its pharmaceutically acceptable salts and 5 to 50 to 50 mg, preferably 508 to 3000 mg of effervescent base. 4, 1, -3. The sparkling composition of claim 1, wherein the sparkling base comprises a mixture of sodium hydrogencarbonate, sodium carbonate and an edible organic acid, The effervescent composition according to claim 4, wherein the effervescent base preferably comprises 50-2000 mg of sodium bicarbonate, 20-200 mg of sodium carbonate and 20-1500 mg of citric acid and / or tartaric acid, 6, Az, 1-3. The sparkling composition of claim 1, wherein the sparkling base is a mixture of calcium carbonate and an edible organic acid. The sparkling composition according to claim 6, characterized in that the sparkling base preferably contains 100-500 mg of calcium ions in the form of C15xoxycarbonate and 20-1500 mg of citric acid and / or its salts, S. 1-3. The sparkling composition of claim 1, wherein the sparkling base comprises mixtures of sodium hydrogencarbonate, sodium carbonate, calcium carbonate and an edible organic acid. The sparkling preparations according to claim 8, characterized in that the sparkling base is preferably 50-500 mg sodium bicarbonate,> 20 ™ 10 mg sodium carbonate, S0-750 mg calcium carbonate and 100-1500 mg citric acid and / or salts thereof. The effervescent composition of claim 1 wherein the edible organic acid is nitric acid, tartaric acid, fumaric acid, adipic acid, succinic acid, ascorbic acid or maleic acid. 11, The shoot. Sparkling formulations according to claim 1, characterized in that the edible organic acid is preferably nitric acid. Sparkling formulations according to claim 1, characterized in that they also contain flavoring agents and sweeteners, as well as known pharmaceutical auxiliaries, such as polyphenylene glycol, sodium benzoate, adipic acid, silicon dioxide. 1 J MUXU. TGR M ρζφη t a 1 ma z o 11: / iWzagh ClOuWé dm aemmsísH tjO'lt-d bless. K. bamusküs ?. AsasAién; t \ sb promise ndtkd milkshake .tmébiy st, s tt Isssitis? · 'stléySá: SetmZOs φ φ φ <· # Φ <Φ ν Φ ** ^χ * X · * φφ <φ φ · φ · The sample contains -10 mg of catirizine * in 80 ml of water Sample B -10 mg cetkizfn * mayminm -apap '80 ml water sample C -10 mg eslirizine + "calcium base" (flavor 1) * 80 ml water sample D - 10 mg cefinzine * "calcium base" (flavor) 2} * 80 ml water